Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxytocin (OT) produced a dose-dependent increase in somatostatin, glucagon and insulin release by isolated mouse islets. A small effect on somatostatin release was observed with 0.1 nM-OT, but 1-10 nM-OT was required to affect A- and B- cells significantly. The effects of OT on somatostatin and glucagon release were similar in the presence of 3 mM- and 10 mM-glucose. No change in insulin release was produced by OT in 3 mM-glucose, but a stimulation was still observed in the presence of a maximally effective concentration of glucose (30 mM). The increase in insulin release produced by OT (in 15 mM-glucose) was accompanied by small accelerations of 86Rb and 45Ca efflux from islet cells. Omission of extracellular Ca2+ accentuated the effect of OT on 86Rb efflux, attenuated that on 45Ca efflux, and abolished that on release. OT never inhibited 86Rb efflux. It did not affect the resting potential of B-cells, but slightly increased the Ca2(+)-dependent electrical activity induced by 15 mM-glucose. OT did not affect cyclic AMP levels, but increased inositol phosphate levels in islet cells. It is suggested that the amplification of glucose-induced insulin release that OT produces is due to a stimulation of phosphoinositide metabolism, and presumably an activation of protein kinase C, rather than to a change in cyclic AMP levels or a direct action on the membrane potential. Since OT is present in the pancreas, it is possible that it exerts a neuropeptidergic control of the islet function.
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PMID:Mechanisms of the stimulation of insulin release by oxytocin in normal mouse islets. 167 63

A major role for Ca2+ and calmodulin in stimulus-secretion coupling has been suggested for several neuropeptides; however, the cellular mechanisms of GH-releasing hormone (GHRH) release have been little investigated so far. We have used a previously validated acute rat hypothalamic explant system in order to elucidate whether Ca2+ acts as a second messenger in the regulation of GHRH release, and whether calmodulin-dependent pathways are involved. Calcium dependence of somatostatin (SRIH) release was assessed in the same experiments. Calmodulin dependence of SRIH was not investigated in detail, as it has been established previously. The calcium-entry antagonist, verapamil, antagonized K(+)-stimulated GHRH and SRIH release in a dose-dependent manner, with maximal inhibition shown at 10(-4) M. The calmodulin antagonist W7 also blocked K(+)-evoked GHRH release in a dose-dependent manner, with significant inhibition in the dose range 5 X 10(-5) M to 2 X 10(-4) M; similarly, a more specific calmodulin inhibitor, the W7 derivative 5-iodo-C8 (W8), reversed K(+)-stimulated GHRH release, showing slightly higher potency than W7. W7 also reversed GHRH release in response to the calcium-ionophore A23187, although verapamil had no effect on A23187-evoked GHRH or SRIH release. Thapsigargin, which increases the efflux of Ca2+ from calciosomes, did not affect either GHRH or SRIH release at 10(-5) M or 10(-4) M. The basal release of GHRH was clearly suppressed by W7 and W8 (10(-4) M), whereas verapamil had no effect. We conclude that calcium influx is crucial for depolarization-induced GHRH and SRIH release. Calcium entrance in response to A23187 appears to be independent of verapamil-sensitive calcium channels. The lack of effect of thapsigargin suggests that increased intracellular Ca2+ from intracellular stores is not equivalent to an increase in Ca2+ influx. Both basal and depolarization-induced release of GHRH in this system are calmodulin dependent.
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PMID:Calcium and calmodulin mediation of growth hormone-releasing hormone release from the rat hypothalamus in vitro. 167 85

The non-pyramidal cells of the hippocampus are heterogeneous with respect to their morphology, peptide content, physiological properties, and postsynaptic targets. Here we demonstrate that the content of peptides (cholecystokinin, somatostatin) and calcium-binding proteins (parvalbumin and calbindin) of non-pyramidal cells is not related to a characteristic fine structure or synaptic input. Varying numbers of GABA-negative and GABA-positive input synapses of non-pyramidal cells indicate that these neurons are differently integrated in inhibitory and disinhibitory circuits.
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PMID:Non-pyramidal cells in the CA3 region of the rat hippocampus: relationships of fine structure, synaptic input and chemical characteristics. 167 25

The study investigated the effects of metformin and phenformin, at "therapeutic" concentrations, on the pancreatic A-, B- and D- cell response to glucose using the isolated perfused rat pancreas model. Changes in the rate of pancreatic lactate output after these biguanides were also evaluated. Metformin--at 1.5 micrograms/ml--and phenformin--at 100 ng/ml--were separately infused both at 160 mg/dl and 300 mg/dl glucose levels. Neither metformin nor phenformin affected glucagon or somatostatin secretion during these two metabolic stimuli with glucose, nor did they significantly influence insulin response to the lower glucose stimulus. Both metformin and phenformin enhanced insulin response to 300 mg/dl glucose infusion and increased the second phase of the B-cell secretory profile but only phenformin significantly enhanced the pancreatic lactate output rate during the 300 mg/dl glucose infusion. Infusion with dichloroacetate (a stimulator of the mitochondrial pyruvate oxidation) or with verapamil (a calcium antagonist) alone did not modify the insulin response to high glucose concentrations. During metformin infusion dichloroacetate neither modified metformin's effects on B-cell response to high glucose nor did it affect the pancreatic lactate output rate. On the other hand dichloroacetate opposed phenformin's effects on the B-cell response to high glucose and reversed the rise in the pancreatic lactate output rate. Verapamil inhibited the effect of metformin on the B-cell response to high glucose but failed to affect phenformin's influence on high-glucose induced insulin release. These data suggest both metformin and phenformin potentiate--at least in rats--the late phase of insulin secretory response to high glucose. However metformin seems to influence pancreatic B-cell activity mainly by facilitating the trans-membrane calcium ion influx responsible for the second phase of insulin release. Phenformin's influence seems indirect since it increases pancreatic lactate production which mediates the enhanced B-cell response to glucose.
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PMID:Do metformin and phenformin potentiate differently B-cell response to high glucose? An in vitro study on isolated rat pancreas. 167 60

The role of signal transduction systems was examined in the secretion of GH-releasing hormone (GHRH) and somatostatin (SS) from perifused rat hypothalamic fragments. Forskolin, an adenylate cyclase activator, stimulated the release of GHRH and SS in a concentration-dependent manner (10-100 microM) with greatest stimulation for GHRH at 100 microM (mean +/- SE, 249 +/- 14%) and for SS at 30 microM (172 +/- 18%). (Bu)2cAMP also augmented GHRH and SS release. The protein kinase-C activator phorbol 12-myristate 13-acetate did not significantly stimulate basal GHRH or SS release at concentrations of 10 nM to 1 microM. The calcium ionophore A23187 enhanced the release of GHRH and SS in a concentration-dependent manner (2-20 microM), with the greatest responses of 282 +/- 50% at 10 microM and 189 +/- 24% at 20 microM, respectively. Potentiation by phorbol 12-myristate 13-acetate of forskolin-stimulated GHRH and SS release was observed. A23187 at 10 microM did not enhance forskolin-stimulated GHRH release, but did potentiate forskolin-stimulated SS release in a more than additive response. We conclude that there is 1) cAMP stimulation of hypothalamic GHRH and SS release, 2) a modulating role of protein kinase-C on cAMP-stimulated release of GHRH and SS, 3) a stimulatory role of the calcium messenger system for GHRH and SS release, 4) interaction of the signal pathways with differences in net GHRH and SS responses, and 5) a modulatory effect of protein kinase-C in perifused hypothalamic fragments which differs from the stimulation of basal GHRH and SS release reported in fetal-derived hypothalamic cell cultures. Our observations suggest an important regulatory role of interacting signal transduction systems in the hypothalamic secretion of GHRH and SS.
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PMID:Signal transduction systems in growth hormone-releasing hormone and somatostatin release from perifused rat hypothalamic fragments. 167 98

To investigate whether somatostatin (SRIF) receptor subpopulations mediate different physiological actions of SRIF, we tested the effects of SRIF and the SRIF agonists MK 678 and CGP 23996 on different biological responses in rat neocortical neurons in culture. Neocortical cells in culture express SRIF receptors that can be labeled with 125I-MK 678 and 125I-CGP 23996. Pharmacological analysis of the binding sites indicates that the radioligands label SRIF receptor subtypes with distinct pharmacological characteristics. These receptor subpopulations are similar to those expressed in adult rat brain. SRIF, MK 678, and CGP 23996 are able to inhibit forskolin-stimulated adenylate cyclase activity in rat neocortical membranes by 25-30%. Furthermore, they inhibit a high voltage-activated Ca2+ current in rat neocortical neurons in culture by 25-35%. Both SRIF and MK 678 potentiate a delayed rectifier K+ current in rat neocortical neurons in culture by 25-30%. In contrast, high concentrations of CGP 23996 do not alter the K+ current. In cells that do not respond to CGP 23996, MK 678 increases the delayed rectifier K+ current. The findings of these studies indicate that rat neocortical neurons in culture express functionally distinct SRIF receptor subtypes that can be differentially activated by SRIF agonists.
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PMID:Subtypes of brain somatostatin receptors couple to multiple cellular effector systems. 167 52

The inhibition of voltage-dependent Ca2+ channels in secretory cells by plasma membrane receptors is mediated by pertussis toxin-sensitive G proteins. Multiple forms of G proteins have been described, differing principally in their alpha subunits, but it has not been possible to establish which G-protein subtype mediates inhibition by a specific receptor. By intranuclear injection of antisense oligonucleotides into rat pituitary GH3 cells, the essential role of the Go-type G proteins in Ca(2+)-channel inhibition is established: the subtypes Go1 and Go2 mediate inhibition through the muscarinic and somatostatin receptors, respectively.
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PMID:Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents. 167 99

The free intracellular calcium ion concentration ([Ca2+]i) was measured in single cells of a population containing 65-80% somatotrophs, using the fluorescent Ca(2+)-indicator Fura-2 and digital imaging microscopy. Spontaneous oscillations in [Ca2+]i ranging in frequency up to 1.5 oscillations per minute were observed in 30% of somatotrophs. These Ca2+ oscillations were blocked by the Ca2+ channel blocker CoCl2 and were thus proposed to be the result of influx of Ca2+ into the cell, possibly as the result of spontaneous electrical activity. GHRH (10-100 nM) increased [Ca2+]i in 61% of the cells studied, although the amplitude and dynamics of the response varied from cell to cell. Typically [Ca2+]i rose from 170 +/- 26 nM to 321 +/- 44 nM (n = 13) in response to a challenge with 66 nM GHRH. GHRH also increased the frequency of Ca2+ oscillations in a number of cells, and some previously quiescent cells showed Ca2+ oscillations following addition of GHRH. Forskolin, which raises cAMP levels in bovine anterior pituitary cells, also stimulated a sustained rise in [Ca2+]i in 10 out of 14 cells tested. Somatostatin (SS) (10-80 nM) rapidly reduced basal [Ca2+]i, blocked Ca2+ oscillations, and blocked the [Ca2+]i response to GHRH. The Ca2+ channel blocker CoCl2 (4 mM) had similar actions on [Ca2+]i to those of SS. These results suggest that GHRH and SS may regulate GH release by modulating Ca2+ entry into the cell through the cell membrane. The [Ca2+]i oscillations seen in a proportion of the somatotrophs were modulated in frequency by GHRH and SS, and are probably generated by influx of Ca2+ through channels in the cell membrane. Thus GH secretion may be regulated by changes in the mean level of [Ca2+]i, which in turn, may be influenced by the frequency of [Ca2+]i oscillations in bovine somatotrophs.
Cell Calcium 1991 Jun
PMID:Calcium homeostasis in bovine somatotrophs: calcium oscillations and calcium regulation by growth hormone-releasing hormone and somatostatin. 167 76

Rat cerebral cortex synaptosomes were exposed in superfusion to various depolarizing stimuli and the release of somatostatin-like immunoreactivity (SRIF-LI) was measured by means of a radioimmunoassay procedure. High KCl (9-50 mM) concentration dependently evoked SRIF-LI release; the evoked overflow reached a plateau at 25 mM KCl and was completely abolished when Ca2+ ions were omitted from the superfusion medium, independently of the concentration of KCl used. The 15 mM K(+)-evoked release of SRIF-LI increased sharply as the Ca2+ concentration was raised to 0.8 mM, then leveled off and reached a plateau at 1.2 mM. The 15 mM K(+)-evoked overflow, but not the spontaneous outflow, was partially decreased (50%) by 1 microM tetrodotoxin. The presence in the superfusion fluid of a mixture of peptidase inhibitors did not improve the recovery of SRIF-LI both in the absence and in the presence of high K+. Exposure of synaptosomes to veratrine (1-50 microM) induced release of SRIF-LI in a concentration-dependent way. The effect of the alkaloid was strictly Ca2+ and tetrodotoxin sensitive. Replacement of extracellular Na+ by sucrose caused an acceleration of the spontaneous SRIF-LI outflow that was inversely correlated to the Na+ content in the superfusion medium. The release evoked by the sodium-deprived media did not exhibit any calcium dependence. HPLC analysis of the samples collected during superfusion showed that greater than 90% of the SRIF-LI released either during the spontaneous outflow or by 15 mM KCl was represented by SRIF-14 (SRIF-28(14-28]. These values reflected the ratio SRIF-14/SRIF-28 found in synaptosomes at the end of the experiments.
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PMID:Somatostatin release from rat cerebral cortex synaptosomes. 168 Jan 60

Adenosine is a potent paracrine/autocrine feedback inhibitor of cell activation in a variety of tissues. Adenosine action was studied in pituitary cells, in which spontaneous electrical activity causes characteristic oscillations of the cytosolic free Ca2+ concentration, [Ca2+]i. Cells of the GH3B6 rat pituitary tumor line were studied by microspectrofluorimetry using the Ca2+ probes indo-1 and fura-2, in part in combination with electrophysiological tight seal whole cell recordings, obtained with the novel approach of patch perforation. It was demonstrated that adenosine receptor activation by N6-(R-phenyl-isopropyl)-adenosine (PIA) caused a block of electrical activity and abolished the ensuing alterations in [Ca2+]i. PIA mimicked the inhibitory action of somatostatin. Adenosine effects are mediated by A1 receptors in these cells and are antagonized by IBMX, an adenosine receptor blocker. PIA also suppressed action potentials that were elicited by the activation of protein kinase C with the phorbol ester PMA, or during the second phase of TRH action. In contrast, no interference was notable on TRH-induced intracellular Ca2+ mobilization. In addition to the abolition of Ca2+ transients, PIA lowers basal [Ca2+]i in some cells. It is proposed that in addition to the inhibition of adenylate cyclase, A1 receptor action on [Ca2+]i is an important element in the control of excitable pituitary cells.
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PMID:Adenosine A1 receptor-induced inhibition of Ca2+ transients linked to action potentials in clonal pituitary cells. 168 Jul 18


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